Selective suppression of IL-12 production by human herpesvirus 6.

Abstract:

:Human herpesvirus 6 (HHV-6) is a potentially immunosuppressive agent that has been suggested to act as a cofactor in the progression of HIV disease. Exposure of human macrophages to HHV-6A or HHV-6B profoundly impaired their ability to produce interleukin 12 (IL-12) upon stimulation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS). By contrast, the production of tumor necrosis factor-alpha (TNF-alpha); regulated on activation, normal T-cell expressed and secreted (RANTES); and macrophage inflammatory protein 1 beta (MIP-1 beta) was not negatively affected. To exclude the involvement of IL-12-suppressive cytokines, such as IL-10 and TNF-alpha, the viral stocks were fractionated by ultra-centrifugation. The bulk of the suppressive activity was recovered within the virion-rich pelleted fraction that was virtually devoid of such cytokines. IL-12 suppression was independent of viral replication, and the effect was not abrogated upon ultraviolet-light inactivation of the viral inoculum. The mechanism of HHV-6-mediated IL-12 suppression was investigated by RNase protection assays, which demonstrated unaltered levels of IL-12 p35 mRNA and only a modest reduction in p40 mRNA, which was insufficient to account for the near-complete loss of both extracellular and intracellular IL-12 protein. Moreover, both the IFN-gamma and the LPS signaling pathways were intact in HHV-6-treated cells. These data suggest that HHV-6 can dramatically affect the generation of effective cellular immune responses, providing a novel potential mechanism of HHV-6-mediated immunosuppression.

journal_name

Blood

journal_title

Blood

authors

Smith A,Santoro F,Di Lullo G,Dagna L,Verani A,Lusso P

doi

10.1182/blood-2002-10-3152

subject

Has Abstract

pub_date

2003-10-15 00:00:00

pages

2877-84

issue

8

eissn

0006-4971

issn

1528-0020

pii

2002-10-3152

journal_volume

102

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Stem cell exhaustion due to Runx1 deficiency is prevented by Evi5 activation in leukemogenesis.

    abstract::The RUNX1/AML1 gene is the most frequently mutated gene in human leukemia. Conditional deletion of Runx1 in adult mice results in an increase of hematopoietic stem cells (HSCs), which serve as target cells for leukemia; however, Runx1(-/-) mice do not develop spontaneous leukemia. Here we show that maintenance of Runx...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-07-232249

    authors: Jacob B,Osato M,Yamashita N,Wang CQ,Taniuchi I,Littman DR,Asou N,Ito Y

    更新日期:2010-02-25 00:00:00

  • Neutralization of tumor necrosis factor activity shortly after the onset of dendritic cell hematopoiesis reveals a novel mechanism for the selective expansion of the CD14-dependent dendritic cell pathway.

    abstract::The CD14-dependent and -independent dendritic cell (DC) pathways are instituted simultaneously when CD34(+) progenitor cells are treated with granulocyte-macrophage colony-stimulating factor (GM-CSF)/tumor necrosis factor (TNF) +/- stem cell factor (SCF) (GTS). If TNF activity is neutralized within 48 hours of cytokin...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Santiago-Schwarz F,McCarthy M,Tucci J,Carsons SE

    更新日期:1998-08-01 00:00:00

  • Mast cells produce interleukin-25 upon Fc epsilon RI-mediated activation.

    abstract::Interleukin-25 (IL-25) is a recently described T helper 2 (T(H)2) cell-derived cytokine that belongs to the IL-17 family and induces the production of IL-4, IL-5, and IL-13 from an unidentified non-T-cell population. Here, we show that mast cells are also potent IL-25-producing cells. When bone marrow-derived mast cel...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-09-2817

    authors: Ikeda K,Nakajima H,Suzuki K,Kagami S,Hirose K,Suto A,Saito Y,Iwamoto I

    更新日期:2003-05-01 00:00:00

  • Third-party CD4+ invariant natural killer T cells protect from murine GVHD lethality.

    abstract::Graft-versus-host disease (GVHD) is driven by extensive activation and proliferation of alloreactive donor T cells causing significant morbidity and mortality following allogeneic hematopoietic cell transplantation (HCT). Invariant natural killer T (iNKT) cells are a potent immunoregulatory T-cell subset in both human...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-11-612762

    authors: Schneidawind D,Baker J,Pierini A,Buechele C,Luong RH,Meyer EH,Negrin RS

    更新日期:2015-05-28 00:00:00

  • Reversion of epigenetically mediated BIM silencing overcomes chemoresistance in Burkitt lymphoma.

    abstract::In Burkitt lymphoma/leukemia (BL), achievement of complete remission with first-line chemotherapy remains a challenging issue, as most patients who respond remain disease-free, whereas those refractory have few options of being rescued with salvage therapies. The mechanisms underlying BL chemoresistance and how it can...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-02-268003

    authors: Richter-Larrea JA,Robles EF,Fresquet V,Beltran E,Rullan AJ,Agirre X,Calasanz MJ,Panizo C,Richter JA,Hernandez JM,Roman-Gomez J,Prosper F,Martinez-Climent JA

    更新日期:2010-10-07 00:00:00

  • The immunoglobulin heavy-chain locus hs3b and hs4 3' enhancers are dispensable for VDJ assembly and somatic hypermutation.

    abstract::The more distal enhancers of the immunoglobulin heavy-chain 3' regulatory region, hs3b and hs4, were recently demonstrated as master control elements of germline transcription and class switch recombination to most immunoglobulin constant genes. In addition, they were shown to enhance the accumulation of somatic mutat...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-12-3827

    authors: Morvan CL,Pinaud E,Decourt C,Cuvillier A,Cogné M

    更新日期:2003-08-15 00:00:00

  • CXCL10-CXCR3 interactions play an important role in the pathogenesis of acute graft-versus-host disease in the skin following allogeneic stem-cell transplantation.

    abstract::Acute graft-versus-host disease (aGVHD) remains a serious complication following allogeneic stem-cell transplantation (SCT), and is mediated by infiltration of alloreactive donor T cells into recipient tissue. Chemokines and their receptors play a central role in controlling the recruitment of T cells into discrete ti...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-12-061408

    authors: Piper KP,Horlock C,Curnow SJ,Arrazi J,Nicholls S,Mahendra P,Craddock C,Moss PA

    更新日期:2007-12-01 00:00:00

  • Programmable 3D silk bone marrow niche for platelet generation ex vivo and modeling of megakaryopoiesis pathologies.

    abstract::We present a programmable bioengineered 3-dimensional silk-based bone marrow niche tissue system that successfully mimics the physiology of human bone marrow environment allowing us to manufacture functional human platelets ex vivo. Using stem/progenitor cells, megakaryocyte function and platelet generation were recor...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-08-595561

    authors: Di Buduo CA,Wray LS,Tozzi L,Malara A,Chen Y,Ghezzi CE,Smoot D,Sfara C,Antonelli A,Spedden E,Bruni G,Staii C,De Marco L,Magnani M,Kaplan DL,Balduini A

    更新日期:2015-04-02 00:00:00

  • Altered erythrocyte endothelial adherence and membrane phospholipid asymmetry in hereditary hydrocytosis.

    abstract::The risk for thrombosis is increased in patients with hereditary hydrocytosis, an uncommon variant of hereditary stomatocytosis. Erythrocytes from 2 patients with hydrocytosis were studied to gain insight into the mechanism of thrombosis in this disorder. Erythrocytes demonstrated abnormal osmotic scan ektacytometry a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2001-12-0329

    authors: Gallagher PG,Chang SH,Rettig MP,Neely JE,Hillery CA,Smith BD,Low PS

    更新日期:2003-06-01 00:00:00

  • In vivo administration of stem cell factor to mice increases the absolute number of pluripotent hematopoietic stem cells.

    abstract::We have examined the effects of administration of stem cell-factor (SCF) on the number and distribution of pluripotent hematopoietic stem cells (PHSC) in normal mice. Using the competitive repopulation assay we found that in vivo administration of SCF increases the absolute number of PHSC per mouse threefold. The incr...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bodine DM,Seidel NE,Zsebo KM,Orlic D

    更新日期:1993-07-15 00:00:00

  • Somatic mosaicism for oncogenic NRAS mutations in juvenile myelomonocytic leukemia.

    abstract::Juvenile myelomonocytic leukemia (JMML) is a rare pediatric myeloid neoplasm characterized by excessive proliferation of myelomonocytic cells. Somatic mutations in genes involved in GM-CSF signal transduction, such as NRAS, KRAS, PTPN11, NF1, and CBL, have been identified in more than 70% of children with JMML. In the...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2012-02-406090

    authors: Doisaki S,Muramatsu H,Shimada A,Takahashi Y,Mori-Ezaki M,Sato M,Kawaguchi H,Kinoshita A,Sotomatsu M,Hayashi Y,Furukawa-Hibi Y,Yamada K,Hoshino H,Kiyoi H,Yoshida N,Sakaguchi H,Narita A,Wang X,Ismael O,Xu Y,Nishio N

    更新日期:2012-08-16 00:00:00

  • Cellular therapies for graft-versus-host disease: a tale of tissue repair and tolerance.

    abstract::The success of allogeneic hematopoietic cell transplantation depends heavily on the delicate balance between the activity of the donor immune system against malignant and nonmalignant cells of the recipient. Abrogation of alloreactivity will lead to disease relapse, whereas untamed allo-immune responses will lead to l...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.2019000951

    authors: Voermans C,Hazenberg MD

    更新日期:2020-07-23 00:00:00

  • Evaluation of mycophenolate mofetil for initial treatment of chronic graft-versus-host disease.

    abstract::We conducted a double-blind, randomized multicenter trial to determine whether the addition of mycophenolate mofetil (MMF) improves the efficacy of initial systemic treatment of chronic graft-versus-host disease (GVHD). The primary endpoint was resolution of chronic GVHD and withdrawal of all systemic treatment within...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1182/blood-2009-02-202937

    authors: Martin PJ,Storer BE,Rowley SD,Flowers ME,Lee SJ,Carpenter PA,Wingard JR,Shaughnessy PJ,DeVetten MP,Jagasia M,Fay JW,van Besien K,Gupta V,Kitko C,Johnston LJ,Maziarz RT,Arora M,Jacobson PA,Weisdorf D

    更新日期:2009-05-21 00:00:00

  • Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients.

    abstract::Whereas the chimeric type I anti-CD20 Ab rituximab has improved outcomes for patients with B-cell malignancies significantly, many patients with non-Hodgkin lymphoma (NHL) remain incurable. Obinutuzumab (GA101) is a glycoengineered, humanized anti-CD20 type II Ab that has demonstrated superior activity against type I ...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2012-01-404368

    authors: Salles G,Morschhauser F,Lamy T,Milpied N,Thieblemont C,Tilly H,Bieska G,Asikanius E,Carlile D,Birkett J,Pisa P,Cartron G

    更新日期:2012-05-31 00:00:00

  • Growth inhibition of a human myeloma cell line by all-trans retinoic acid is not mediated through downregulation of interleukin-6 receptors but through upregulation of p21(WAF1).

    abstract::All-trans retinoic acid (ATRA) has previously been shown to inhibit the growth of OPM-2 human myeloma cells. The growth inhibition was postulated to result from a transcriptional downregulation of interleukin-6 receptor alpha (IL-6Ralpha) with IL-6Rbeta (gp130) unaffected. To formally test this hypothesis, an expressi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chen YH,Lavelle D,DeSimone J,Uddin S,Platanias LC,Hankewych M

    更新日期:1999-07-01 00:00:00

  • Asymptomatic hemochromatosis subjects: genotypic and phenotypic profiles.

    abstract::Screening for hereditary hemochromatosis (HHC) by means of transferrin saturation (TS) levels has been advocated and will identify many patients who are asymptomatic. The purposes of this study were (1) to determine HFE genotypes among asymptomatic HHC patients and correlate this profile with the degree of iron overlo...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Sham RL,Raubertas RF,Braggins C,Cappuccio J,Gallagher M,Phatak PD

    更新日期:2000-12-01 00:00:00

  • The clinical significance of EBV DNA in the plasma and peripheral blood mononuclear cells of patients with or without EBV diseases.

    abstract::Epstein-Barr virus (EBV) is a ubiquitous virus that establishes a latent infection within the host and in some cases can lead to the development of EBV-associated lymphomas, lymphoproliferative disorders, hemophagocytic lymphohistiocytosis, solid tumors, and other diseases. We studied the clinical significance of dete...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2015-09-672030

    authors: Kanakry JA,Hegde AM,Durand CM,Massie AB,Greer AE,Ambinder RF,Valsamakis A

    更新日期:2016-04-21 00:00:00

  • Microbiologically documented infections and infection-related mortality in children with acute myeloid leukemia.

    abstract::The primary objective was to describe the prevalence and characteristics of microbiologically defined infections and infection-related mortality (IRM) in 492 children with acute myeloid leukemia enrolled on CCG 2961. Secondary objectives were to determine the relationship between demographic, disease-related, and ther...

    journal_title:Blood

    pub_type: 杂志文章,多中心研究

    doi:10.1182/blood-2007-05-091942

    authors: Sung L,Lange BJ,Gerbing RB,Alonzo TA,Feusner J

    更新日期:2007-11-15 00:00:00

  • A broad T-cell repertoire diversity and an efficient thymic function indicate a favorable long-term immune reconstitution after cord blood stem cell transplantation.

    abstract::Cord blood (CB) is used increasingly as a source of hematopoietic stem cells because of a lower risk of acute and chronic graft-versus-host disease (GVHD). However, there is some concern regarding the ability to adequately reconstitute host immune response due to the immaturity and naivety of CB T cells. This study wa...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v99.4.1458

    authors: Talvensaari K,Clave E,Douay C,Rabian C,Garderet L,Busson M,Garnier F,Douek D,Gluckman E,Charron D,Toubert A

    更新日期:2002-02-15 00:00:00

  • Regulation of endothelial thrombomodulin expression by inflammatory cytokines is mediated by activation of nuclear factor-kappa B.

    abstract::Inflammation and thrombosis are increasingly recognized as interrelated biologic processes. Endothelial cell expression of thrombomodulin (TM), a key component of the anticoagulant protein C pathway, is potently inhibited by inflammatory cytokines. Because the mechanism underlying this effect is largely unknown, we in...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-03-0928

    authors: Sohn RH,Deming CB,Johns DC,Champion HC,Bian C,Gardner K,Rade JJ

    更新日期:2005-05-15 00:00:00

  • Th1 and Th2 T-helper cells exert opposite regulatory effects on procoagulant activity and tissue factor production by human monocytes.

    abstract::The role of T-cell subsets in the induction of tissue factor (TF) production by human monocytes in vitro was investigated. Mitogen stimulation enabled both unfractionated T cells and their CD4+ or CD8+ subsets to promote procoagulant activity (PCA). After mitogen or antigen activation, all seven T-cell clones with Th1...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Del Prete G,De Carli M,Lammel RM,D'Elios MM,Daniel KC,Giusti B,Abbate R,Romagnani S

    更新日期:1995-07-01 00:00:00

  • Lymphoid apoptosis and myeloid hyperplasia in CCAAT displacement protein mutant mice.

    abstract::CCAAT displacement protein (cux/CDP) is an atypical homeodomain protein that represses expression of several developmentally regulated lymphoid and myeloid genes in vitro, including gp91-phox, immunoglobulin heavy chain, the T-cell receptor beta and gamma chains, and CD8. To determine how this activity affects cell de...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.13.3658

    authors: Sinclair AM,Lee JA,Goldstein A,Xing D,Liu S,Ju R,Tucker PW,Neufeld EJ,Scheuermann RH

    更新日期:2001-12-15 00:00:00

  • Proteolytic inactivation of ADAMTS13 by thrombin and plasmin.

    abstract::The multimeric size and the function of circulating von Willebrand factor are modulated via its proteolytic cleavage by the plasma metalloproteinase, ADAMTS13. It is unclear how ADAMTS13 activity is regulated within the vascular system. In the absence of a regulatory mechanism, ADAMTS13 activity might compromise plate...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2004-03-1101

    authors: Crawley JT,Lam JK,Rance JB,Mollica LR,O'Donnell JS,Lane DA

    更新日期:2005-02-01 00:00:00

  • Stat3 signaling in acute myeloid leukemia: ligand-dependent and -independent activation and induction of apoptosis by a novel small-molecule Stat3 inhibitor.

    abstract::Acute myeloid leukemia (AML) is an aggressive malignancy with a relapse rate approaching 50%, despite aggressive chemotherapy. New therapies for AML are targeted at signal transduction pathways known to support blast survival, such as the Stat3 pathway. Aberrant activation of Stat3 has been demonstrated in many differ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-04-280123

    authors: Redell MS,Ruiz MJ,Alonzo TA,Gerbing RB,Tweardy DJ

    更新日期:2011-05-26 00:00:00

  • Fas antigen expression on CD34+ human marrow cells is induced by interferon gamma and tumor necrosis factor alpha and potentiates cytokine-mediated hematopoietic suppression in vitro.

    abstract::Activation of Fas antigen, a cell surface receptor molecule, by its ligand results in transduction of a signal for cell death. The Fas system has been implicated in target cell recognition, clonal development of immune effector cells, and termination of the cellular immune response. Fas antigen expression on lymphocyt...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Maciejewski J,Selleri C,Anderson S,Young NS

    更新日期:1995-06-01 00:00:00

  • A noncoding antisense RNA in tie-1 locus regulates tie-1 function in vivo.

    abstract::Recently, messenger RNAs in eukaryotes have shown to associate with antisense (AS) transcript partners that are often referred to as long noncoding RNAs (lncRNAs) whose function is largely unknown. Here, we have identified a natural AS transcript for tyrosine kinase containing immunoglobulin and epidermal growth facto...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-09-242180

    authors: Li K,Blum Y,Verma A,Liu Z,Pramanik K,Leigh NR,Chun CZ,Samant GV,Zhao B,Garnaas MK,Horswill MA,Stanhope SA,North PE,Miao RQ,Wilkinson GA,Affolter M,Ramchandran R

    更新日期:2010-01-07 00:00:00

  • Cytomegalovirus reactivation after allogeneic transplantation promotes a lasting increase in educated NKG2C+ natural killer cells with potent function.

    abstract::During mouse cytomegalovirus (CMV) infection, a population of Ly49H(+) natural killer (NK) cells expands and is responsible for disease clearance through the induction of a "memory NK-cell response." Whether similar events occur in human CMV infection is unknown. In the present study, we characterized the kinetics of ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-10-386995

    authors: Foley B,Cooley S,Verneris MR,Pitt M,Curtsinger J,Luo X,Lopez-Vergès S,Lanier LL,Weisdorf D,Miller JS

    更新日期:2012-03-15 00:00:00

  • Felic (CIP4b), a novel binding partner with the Src kinase Lyn and Cdc42, localizes to the phagocytic cup.

    abstract::Through its Src homology 3 (SH3) and SH2 domains, the Src kinase Lyn interacts with a small number of phosphoproteins, such as Shc, Cbl, and Vav, which regulate cell cycle and the cytoskeleton. Using Lyn's Unique, SH3, and SH2 domains as bait in a yeast 2-hybrid screen, we isolated a novel gene product with features o...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-03-0851

    authors: Dombrosky-Ferlan P,Grishin A,Botelho RJ,Sampson M,Wang L,Rudert WA,Grinstein S,Corey SJ

    更新日期:2003-04-01 00:00:00

  • EPO-mediated expansion of late-stage erythroid progenitors in the bone marrow initiates recovery from sublethal radiation stress.

    abstract::Erythropoiesis is a robust process of cellular expansion and maturation occurring in murine bone marrow and spleen. We previously determined that sublethal irradiation, unlike bleeding or hemolysis, depletes almost all marrow and splenic erythroblasts but leaves peripheral erythrocytes intact. To better understand the...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2011-11-394304

    authors: Peslak SA,Wenger J,Bemis JC,Kingsley PD,Koniski AD,McGrath KE,Palis J

    更新日期:2012-09-20 00:00:00

  • Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load.

    abstract::Primary infection with the human herpesvirus, Epstein-Barr virus (EBV), may result in subclinical seroconversion or may appear as infectious mononucleosis (IM), a lymphoproliferative disease of variable severity. Why primary infection manifests differently between patients is unknown, and, given the difficulties in id...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v98.13.3739

    authors: Silins SL,Sherritt MA,Silleri JM,Cross SM,Elliott SL,Bharadwaj M,Le TT,Morrison LE,Khanna R,Moss DJ,Suhrbier A,Misko IS

    更新日期:2001-12-15 00:00:00